Association of myostatin deficiency with collagen related disease-umbilical hernia and tippy toe standing in pigs

Paek, Hyo-Jin; Luo, Zhao‐Bo; Choe, Hak Myong; Quan, Biao-Hu; Gao, Kai; Han, Sheng-Zhong; Li, Zhou-Yan; Kang, Jin‐Dan; Yin, Xi‐Jun

doi:10.1007/s11248-021-00275-6

Cited by 8 publications

(3 citation statements)

References 47 publications

(60 reference statements)

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“…In a study of MSTN knockout cattle, Smad2/3 bound to TET1 to regulate the DNA methylation modification to regulate the expression of myogenic factors to control muscle size [ 61 ], and it can also bind to the PDE5A promoter region to regulate glucose metabolism in the myocardium [ 25 ]. In Mstn −/− pigs, the reduction of Smad2/3 inhibited the atrophic effect of activin receptor-like kinase 5 (ALK5) [ 62 ]. Smad can bind to the promoter sequence of target genes and regulate gene transcription activity, thereby affecting gene expression.…”

Section: Discussionmentioning

confidence: 99%

Loss of Myostatin Alters Mitochondrial Oxidative Phosphorylation, TCA Cycle Activity, and ATP Production in Skeletal Muscle

Wang

Wei

et al. 2022

IJMS

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Myostatin (MSTN) is an important negative regulator of skeletal muscle growth in animals. A lack of MSTN promotes lipolysis and glucose metabolism but inhibits oxidative phosphorylation (OXPHOS). Here, we aimed to investigate the possible mechanism of MSTN regulating the mitochondrial energy homeostasis of skeletal muscle. To this end, MSTN knockout mice were generated by the CRISPR/Cas9 technique. Expectedly, the MSTN null (Mstn−/−) mouse has a hypermuscular phenotype. The muscle metabolism of the Mstn−/− mice was detected by an enzyme-linked immunosorbent assay, indirect calorimetry, ChIP-qPCR, and RT-qPCR. The resting metabolic rate and body temperature of the Mstn−/− mice were significantly reduced. The loss of MSTN not only significantly inhibited the production of ATP by OXPHOS and decreased the activity of respiratory chain complexes, but also inhibited key rate-limiting enzymes related to the TCA cycle and significantly reduced the ratio of NADH/NAD+ in the Mstn−/− mice, which then greatly reduced the total amount of ATP. Further ChIP-qPCR results confirmed that the lack of MSTN inhibited both the TCA cycle and OXPHOS, resulting in decreased ATP production. The reason may be that Smad2/3 is not sufficiently bound to the promoter region of the rate-limiting enzymes Idh2 and Idh3a of the TCA cycle, thus affecting their transcription.

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Section: Discussionmentioning

confidence: 99%

Loss of Myostatin Alters Mitochondrial Oxidative Phosphorylation, TCA Cycle Activity, and ATP Production in Skeletal Muscle

Wang

Wei

et al. 2022

IJMS

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“…One of these MSTN -edited models, its progeny, or its crosses were further investigated . These include investigations on fiber-type distribution and expression of myosin heavy chain isoforms; shift from slow- to fast-twitch muscle fibers in skeletal muscle; internal organ size; semen quality and fertilization ability; reproductive trait characterization in MSTN -edited crosses; collagen-related pathological features (umbilical hernia and tippy toe standing); regulation of body fat deposition; fibrinogen levels and fibrin clot structure; esophageal striated muscle development and regulation of muscle fiber types; extraocular muscles; cardiac extracellular matrix; growth of smooth muscle in uterine horns of MSTN mutant gilts; smooth muscle content in corpus cavernosum of MSTN mutant boars; erythrocyte osmotic fragility, hematological parameters, and fatty acid composition of serum and erythrocyte membranes; miR-455-3p regulation of myoblast differentiation; composition and alteration of gut microbiota; analysis of meat and fatty acids characteristics; and development of a restriction enzyme-mediated PCR-RFLP assay for genotyping MSTN mutant pigs …”

Section: Targeting the Mstn Gene In Pigsmentioning

confidence: 99%

When Less Is More: Targeting the Myostatin Gene in Livestock for Augmenting Meat Production

Kalds

Zhou

Huang

et al. 2023

J. Agric. Food Chem.

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How to increase meat production is one of the main questions in animal breeding. Selection for improved body weight has been made and, due to recent genomic advances, naturally occurring variants that are responsible for controlling economically relevant phenotypes have been revealed. The myostatin (MSTN) gene, a superstar gene in animal breeding, was discovered as a negative controller of muscle mass. In some livestock species, natural mutations in the MSTN gene could generate the agriculturally desirable double-muscling phenotype. However, some other livestock species or breeds lack these desirable variants. Genetic modification, particularly gene editing, offers an unprecedented opportunity to induce or mimic naturally occurring mutations in livestock genomes. To date, various MSTN-edited livestock species have been generated using different gene modification tools. These MSTN gene-edited models have higher growth rates and increased muscle mass, suggesting the high potential of utilizing MSTN gene editing in animal breeding. Additionally, post-editing investigations in most livestock species support the favorable influence of targeting the MSTN gene on meat quantity and quality. In this Review, we provide a collective discussion on targeting the MSTN gene in livestock to further encourage its utilization opportunities. It is expected that, shortly, MSTN gene-edited livestock will be commercialized, and MSTN-edited meat will be on the tables of ordinary customers.

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“…Since Wang et al [ 45 ] suggested that commercial breeds would be more sensitive to the KO of endogenous genes, Zou et al [ 46 ] generated two healthy Duroc pigs with the Belgian Blue mutation only in heterozygosity, but they did not show double muscling at the neonatal stage. It could be explained by a recent finding that showed in commercial MSTN KO pigs, the decreased expression level of type I collagen and Scleraxis, could result in umbilical hernia and tippy-toe standing problems typified by the tendon and linea alba dysfunction [ 47 ].…”

Section: Application Of New Breeding Technology In Pig Productionmentioning

confidence: 99%

The application of new breeding technology based on gene editing in pig industry — A review

Chuang

Yang

2022

Anim Biosci

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Genome/gene-editing (GE) techniques, characterized by a low technological barrier, high efficiency, and broad application among organisms, are now being employed not only in medical science but also in agriculture/veterinary science. Different engineered CRISPR/Cas9s have been identified to expand the application of this technology. In pig production, GE is a precise new breeding technology (NBT), and promising outcomes in improving economic traits, such as growth, lean or healthy meat production, animal welfare, and disease resistance, have already been documented and reviewed. These promising achievements in porcine gene editing, including the Myostatin gene knockout (KO) in indigenous breeds to improve lean meat production, the uncoupling protein 1 (UCP1) gene knock-in to enhance piglet thermogenesis and survival under cold stress, the generation of GGTA1 and CMAH gene double KO pigs to produce healthy red meat, and the KO or deletion of exon 7 of the CD163 gene to confer resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection, are described in the present article. Other related approaches for such purposes are also discussed.The current trend of global regulations or legislation for GE organisms is that they are exempted from classification as genetically modified organisms (GMOs) if no exogenes are integrated into the genome, according to product-based and not process-based methods. Moreover, an updated case study in the EU showed that current GMO legislation is not fit for purpose in term of NBTs, which contribute to the objectives of the EU's Green Deal and biodiversity strategies A c c e p t e d A r t i c l e 4 and even meet the United Nations' sustainable development goals for a more resilient and sustainable agri-food system. The GE pigs generated via NBT will be exempted from classification as GMOs, and their global valorization and commercialization can be foreseen.

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Association of myostatin deficiency with collagen related disease-umbilical hernia and tippy toe standing in pigs

Cited by 8 publications

References 47 publications

Loss of Myostatin Alters Mitochondrial Oxidative Phosphorylation, TCA Cycle Activity, and ATP Production in Skeletal Muscle

Loss of Myostatin Alters Mitochondrial Oxidative Phosphorylation, TCA Cycle Activity, and ATP Production in Skeletal Muscle

When Less Is More: Targeting the Myostatin Gene in Livestock for Augmenting Meat Production

The application of new breeding technology based on gene editing in pig industry — A review

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